Liposomes are under investigation as carriers of 2'3'- dideoxynucleotides (ddNTs) in an effort to enhance the activity of these compounds against the human immunodeficiency virus (HIV). Although it is the ddNTs which actually block viral replication by inhibition of HIV-reverse transcriptase (HIV-RT), only their precursors, the 2'3'-dideoxynucleosides (ddNSs), can be used clinically since ddNTs are unstable in the presence of serum and are not readily taken up by cells. Dideoxycytidine triphosphate (ddCTP), the active anabolite of dideoxycytidine (ddCyt), was found to increase anti-HIV activity when entrapped in liposomes as compared to the free compound. Furthermore, the degradation of ddCTP by serum components was significantly decreased when the compound was entrapped in liposomes. Unlike other ddNSs tested, dideoxyuridine (ddUrd) was found to be devoid of anti-HIV activity, although its corresponding ddNT, 2,3'dideoxyuridine triphosphate (ddUTP), was shown to be a potent inhibitor of HIV-RT. Liposome- entrapped ddUTP is currently being tested for anti-HIV activity. These findings suggest that ddNTs, which are inappropriate for clinical usage for the reasons stated above, could be useful when administered as liposome-entrapped agents.